Analysis of gene variation and clinical characteristics of Wiedemann-Steiner syndrome / 中华儿科杂志

Objective: To summarize and analyze the clinical characteristics and gene mutations of 6 patients with Wiedemann-Steiner syndrome (WDSTS). Methods: To review and analyze the clinical data, including general conditions, clinical manifestations, growth hormone, cranial or pituitary gland magnetic resonance imaging (MRI),gene results and other data, 6 cases with WDSTS admitted to the Department of Endocrinology, Genetics and Metabolism of Jiangxi Provincial Children's Hospital and the Department of Child Care of Pingxiang Maternity and Child Care from April 2017 to February 2021 were recruited. Results: Of the 6 patients, 2 were male and 4 were female. The age of the first visit ranged from 1.0 to 11.2 years. All the 6 children presented with growth retardation and mental retardation and they all had typical facial dysmorphism and hypertrichosis (mainly on the back and limbs). Among them, case 5 had a growth hormone deficiency, and case 2 and 4 had abnormalities revealed by cranial MRI. Variations in KMT2A gene were identified in these 6 patients: c.10900+2T>C,c.10837C>T(p.Gln3613*), c.4332G>A(p.E1444E), c.2508dupC(p.W838Lfs*9), c.11695_11696delinsT(p.T3899Sfs*73), c.9915dupA (p.P3306Tfs*22).Among these variations, c.4332G>A, c.11695_11696delinsT and c.9915dupA were novel mutations. Therefore, the final diagnosis of these patients was WDSTS. Conclusions: Patients presented with short stature and mental retardation, typical facial dysmorphism and hypertrichosis should be considered WDSTS. Whole-exome sequencing plays an important role in disease diagnosis and genetic counseling.

Wiedemann-Steiner syndrome with a novel pathogenic variant in KMT2A: a case report / Síndrome de Wiedemann-Steiner por una nueva variante patogénica en KMT2A: reporte de un caso

Abstract Case Description: We report the case of a one-year-old girl who was diagnosed with Wiedemann-Steiner Syndrome based on the identification of a novel de novo frameshift mutation in the KMT2A gene by whole exome sequencing and supported by her clinical features. Clinical Findings: KMT2A mutations cause Wiedemann-Steiner Syndrome, a very rare genetic disorder characterized by congenital hypertrichosis, short stature, intellectual disability, and distinct facial features. Treatment and Outcome: Whole exome sequencing identified a novel frameshift variant: c. 4177dupA (p.Ile1393Asnfs * 14) in KMT2A; this change generates an alteration of the specific binding to non-methylated CpG motifs of the DNA to the protein. The genotype and phenotype of the patient were compared with those of earlier reported patients in the literature. Clinical Relevance: In diseases with low frequency, it is necessary to establish a genotype-phenotype correlation that allows the establishment of therapeutic and follow-up goals. The phenotype comparation with other reported cases did not show differences attributable to sex or age among patients with Wiedemann-Steiner Syndrome. Whole exome sequencing allows identifying causality in conditions with high clinical and genetic heterogeneity like hypertrichosis.

Resumen Descripción del caso: Se reporta el caso de una paciente femenina de un año de edad, diagnosticada con Síndrome de Wiedemann-Steiner basado en la identificación de una nueva variante patogénica de novo de tipo frameshift en el gen KMT2A Mediante secuenciación de exoma usando el enfoque de trio, sumado a sus características clínicas. Hallazgos clínicos: las mutaciones en KMT2A causan el Síndrome de Wiedemann-Steiner, un desorden genético muy raro caracterizado por hipertricosis congénita, talla baja, retardo mental variable y fenotipo facial distintivo, los cuales se encuentran en la paciente reportada. Resultado: La Secuenciación de exoma completo encontró una variante de tipo frameshift: c.4177dupA (p. Ile1393Asnfs * 14) en KMT2A, este cambio a nivel génico genera una alteración de la unión específica a motivos CpG no metilados del DNA a la proteína. El genotipo y el fenotipo de la paciente fue comparado con los pacientes reportados previamente en la literatura. Relevancia clínica: En enfermedades con baja frecuencia como la aquí reportada es necesario establecer correlaciones genotipo-fenotipo que permitan establecer planes terapéuticos y de seguimiento. El análisis realizado no evidenció diferencias atribuibles a sexo o edad entre los pacientes diagnosticados con Síndrome de Weidemann-Steiner. La secuenciación de exoma permitió identificar causalidad en este caso, cuya característica principal de hipertricosis se asocia con alta heterogeneidad clínica y genética.

Do you know this syndrome? Dyspigmentation along the Blaschko lines caused by trisomy 7 mosaicism

Abstract Dyspigmentation along the Blaschko lines is strongly suggestive of a mosaic skin disorder. We report a 9-year-old male patient who presented with swirls and streaks of both hypo and hyperpigmentation involving the entire body. Additionally, he had hypertrichosis, musculoskeletal and minor neurodevelopment abnormalities but no intellectual disability. Cultured fibroblast displayed trisomy 7 mosaicism, which can explain this pigmentary phenotype. Widespread dyspigmentation associated with involvement of other organs should prompt systemic examination to detect additional anomalies and genetic evaluation should be considered, even with normal fetal karyotype.

Síndrome H: primer caso pediátrico reportado en América Latina / H syndrome: First reported paediatric case in Latin America

Introducción: El síndrome H es una enfermedad genética extremadamente rara de compromiso multisistémico, el cual clínicamente puede ser reconocido de forma precoz, ofreciendo de manera oportuna un seguimiento, tratamiento específico y asesoramiento genético. Objetivo: Presentar un caso con características «típicas del síndrome H¼ para favorecer su identificación precoz. Caso clínico: Varón de 8 años de edad, evaluado por tumoraciones testiculares, lesiones dérmicas tipo hiperpigmentación con hipertricosis, retraso del lenguaje, talla baja, deformidades articulares, hipoacusia neurosensorial bilateral, anemia, hipergammaglobulinemia y alteraciones óseas. En los estudios histológicos de la piel y las masas testiculares se observó infiltración linfoplasmocitaria. El secuenciamiento del gen SLC29A3 detectó una mutación homocigota c.1087 C>T (p.Arg363Trp; rs387907067) concluyente con el síndrome H, la cual ha sido reportada previamente. Conclusiones: Este es el primer caso reportado en Latinoamérica del síndrome H, cuyas características descritas son parte del espectro clínico. El hallazgo clínico principal, que orienta al diagnóstico, es la hiperpigmentación acompañada de hipertricosis.

Introduction: H Syndrome is an extremely rare genetic disease, with a multisystemic character and which can be identified in early childhood, offering the opportunity of specific treatment and genetic counselling. Objective: To present a clinical case with "typical" characteristics of H Syndrome. Clinical case: The case is presented of an 8-year-old male patient who presented with testicular tumours and skin lesions characterised by hyperpigmentation with hypertrichosis, language delay, short stature, and joint deformities. He also presented with bilateral sensorineural hearing loss, anaemia, hypergammaglobulinaemia, and bone disorders. Histopathology studies of the skin and testicular masses reported lymphoplasmacytic infiltration. Sequencing analysis of gene SLC29A3 showed the homozygote mutation c.1087 C>T (p.Arg363Trp; rs387907067). Conclusions: These findings are consistent with H syndrome, and this is the first reported case in Latin America. The key to the diagnosis is the finding of hyperpigmentation with hypertrichosis.

Do you know this syndrome? / Você conhece esta síndrome?

Congenital Hypertrichosis Lanugionsa is a rare autosomal dominant genetic disorder, with fewer than 50 cases reported in the literature. It is characterized by excessive lanugo hair, sparing only the mucous membranes, palms and soles. It may be associated with other organic abnormalities and should form part of the dermatologist's current knowledge. We discuss some aspects of the syndrome in question arising from the case report of a 2-year-old female patient, black, with classic clinical presentation, with no other associated congenital abnormalities.

A hipertricose Lanugionsa Congênita é uma desordem genética rara, autossômica dominante, com menos de 50 casos descritos na literatura. É caracterizada por pêlo lanugo excessivo, poupando apenas membranas mucosas, palmas e plantas. Pode estar associada a outras anormalidades orgânicas, devendo ser de conhecimento do dermatologista. Discutiremos aspectos da síndrome em questão a partir do relato de caso de uma paciente do sexo feminino, negra, 02 anos, com apresentação clínica clássica, sem outras anormalidades congênitas associadas.

Sindrome de Lipodistrofia Congénita Generalizada / Congenital generalized lipodystrophy syndrome

El actual estudio trata sobre la forma de presentación y evolución de los pacientes con lipodistrofia congénita generalizada o el Síndrome de Seip-Berardinelli. Se caracteriza por la ausencia de tejido graso subcutáneo, cirrosis hepática, desarrollo de diabetes resistente a la insulina, hiperlipemia, y crecimiento corporal rápido con edad ósea avanzada en la infancia, coexistiendo alteraciones cutáneas, desarrollo muscular exagerado y compromiso de otros órganos. Se presentan 3 casos de esta patología diagnosticados entre 9 y 19 meses de edad. Las 3 pacientes presentaban varias características en común: aparentaban una edad mayor a la cronlógica, cara triangular, abundante cabello, lesiones hiperpigmentadas a predominio de pliegues, marcada disminución de tejido celular subcutáneo, prominencia muscular y hepatomegalia. Otros hallazgos clínicos sólo se demostraron en una u otra de las pacientes. La evaluación de laboratorio muestra alteración precoz de lípidos a predominio de triglicéridos, conservando la glicemia y la curva de tolerancia a la glucosa dentro de límites normales. Edad ósea avanzada en 1 de los 3 casos. Analizando los datos de las pacientes y de la literatura respecto a la fisiopatología y posibles efectos beneficiosos de los neurolépticos, se sugiere existencia de alguna anomalía a nivel del hipotálamo y/o hipófisis responsable de la presentacióm del cuadro clínico.